In this application, we propose to characterize a novel blood biomarker of Alzheimer's disease (AD). We previously demonstrated in a pilot study that the dynamic changes in plasma amyloid-beta (A?) levels after administration of an OGTT (hitherto referred to as ?A?-OGTT??) differentiates mild cognitive impairment (MCI) subjects from clinically normal (CN) subjects. In this proposal, we will demonstrate the following: (i) A?-OGTT? can also differentiate AD subjects from CN subjects; (ii) A?-OGTT? is associated with brain A? burden on Pittsburg Compound B-Positron Emission Tomography (PiB-PET); (iii) the mechanism of A?-OGTT? may be due to the role of A?-binding proteins (chaperones). In a cross-sectional study, we will administer OGTT to a group of individuals in each of the MCI, AD and CN groups. Plasma samples will be obtained at various time points after the administration of OGTT. Plasma samples will be quantified for A? 40, 42, and A? binding proteins. A?-OGTT? value will be calculated for all groups to determine if there are differences among the three groups. A?-OGTT? value will also be correlated with A? burden on PiB-PET in CN to determine if the plasma biomarker is reflective of the underlying pathology in a preclinical population. Finally, A?-OGTT? value will be correlated with A? binding protein levels. The results of this proposal will provide data regarding the potential utility of A?-OGTT? as a diagnostic biomarker of MCI and AD, as well as a biomarker of underlying disease state. It will also provide data on the potential relationship between plasma A? 40 and 42 levels and A? binding proteins, and whether there may be a more efficient clearance of A? in NC. In addition, the data from this proposal will enable us to gather sufficient data to design a longitudinal study to demonstrate the utility of A?-OGTT? in differentiating subjects, predict disease progression, and monitor therapeutic response.